A large body of evidence exists which implicates enterotoxin-producing Escherichia coli as the cause of a high percentage of undiagnosed diarrheas in man. Enterotoxigenic E. coli from animal sources have been found to produce an additional virulence factor -- species-specific, surface-associated antigens (K88,K99) which confer the ability to colonize the small bowel of certain animals. These K antigens also have mannose-resistant hemagglutinin activity (MR-HA). Using a pair of isogenic strains 334 (LT plus/ST plus, MR-HA plus buccal adherent) and 334 (LT minus ST minus, HA minus bucca non-adherent) we have been able to isolate the specific MR-HA receptor which we term specific 334 MR-HA pili. Examination by electron microscopy revealed the presence of an apparently homogenous para-crystalline material. This preparation was used to produce antisera against the specific MR-HA pili. Using the buccal assay, MR-HA of various blood cells and reactivity with specific pili antisera, we have detected adherent strains which have differing adherence antigens. Presumably, these strains attach to buccal cells by different pili or non-pili components. ETEC strains from man will be compared in their ability to adhere to human mucosal epithelial cells, human fetal intestinal cells in tissue culture and to the small bowel of infant rabbits in order to develop specific adherence assays for toxigenic E. coli. The physiologic and genetic control of adherence antigens will be investigated along with a study of their biological properties. Greater understanding of the adherence antigens present on toxigenic E. coli from humans will then allow the development of specific "blocking" or competing substance(s) designed to interfere with bacterial colonization.